Chromopancreatoscopy for preoperative evaluation of main duct intraductal pancreatic mucinous neoplasm. First in Human. Case Report. Chromoendoscopy involves the application of dyes, stains, or pigments to improve tissue localization, characterization, and diagnostic yield. Chromoendoscopy has been studied in the setting of luminal mucosal disease such as endoscopic screening in patients with ulcerative colitis, further characterization of colonic polyps, etc. Preoperative evaluation of main duct IPMN via pancreatoscopy allows clinicians to determine anatomical areas of involvement and better plan organ-sparing surgery. Determining the lateral borders of the lesion during pancreatoscopy is essential, but can be challenging when there is active ductal inflammation in cases such as pre-existing stents, etc. The use of dye-based pancreatoscopy has not yet been clinically described or evaluated. We present a 59-year-old male who was referred for further evaluation of a dilated main pancreatic duct. The patient denied a history of alcohol use, tobacco use, a personal or family history of pancreatic disease, abnormal liver chemistries, or abdominal pain. After undergoing an endoscopic ultrasound at an outside facility, he was advised to undergo a total pancreatectomy for main duct IPMN. He presented to our facility for a second opinion. On MRI, the main pancreatic duct appeared normally sized in the pancreatic head and was significantly dilated beyond the pancreatic neck. There were no clearly visualized intra- or periductal lesions at the transition point. On CT scan, we note mild atrophy of the pancreatic body and tail, with no parenchymal or intraductal calcifications. After a multidisciplinary discussion with our medical and surgical pancreatology team, we decided to proceed with repeat endoscopy for histological diagnosis and preoperative staging. Endoscopy was performed in a prone position under general anesthesia. On endoscopic ultrasound, the PD appeared normally sized in the pancreatic head with diffused dilatation beyond the pancreatic neck where it measured 11 mm. There were no sonographically visualized lesions at the transition point. We proceeded with ERCP with the intention of performing pancreatoscopy with biopsies. As seen here, the papilla did not have a classic fish-mouth appearance that is oftentimes seen in patients with IPMN. The ventral duct was cannulated without difficulty. On pancreatogram, the main pancreatic duct appeared unremarkable in the head of the pancreas with diffuse enlargement in the body and the tail. The transition point appeared to be in the pancreatic neck. Given the perceived inability to pass a cholangioscope through the ansa loop, it was decided to use the dorsal duct as a more direct route to evaluate the transition point located in the neck of the pancreas. After several failed attempts at cannulating the dorsal duct, we decided to use a double-wire rendezvous technique. The ventral duct was once again cannulated using a curved soft-tip guide wire. The wire was subsequently advanced into the dorsal duct and across the minor papilla in an anterograde fashion. The wire was then advanced into the duodenum where it was coiled several times and the sphinctrotome was withdrawn. Keeping the first or rendezvous wire in place, the dorsal duct was cannulated by railroading a modified sphinctrotome over the rendezvous wire and a second wire was advanced into the main pancreatic duct. Minor papillotomy was performed and an 8.5 French plastic pancreatic stent was then placed across the minor papilla into the main pancreatic duct. Following this, the patient was discharged home uneventfully. On repeat ERCP four weeks later, the pancreatic stent was removed and the main pancreatic duct was cannulated over a guide wire using a standard cholangioscope. On pancreatoscopy, multiple fish-egg-like projections were visualized in the proximal 2 cm of the main pancreatic duct. The remainder of the main pancreatic duct appeared diffusely erythematous with fibrinous exudates likely due to the previously placed pancreatic stent. Due to the underlying inflammation, we were unable to clearly identify margins of the IPMN and exclude skipped lesions. We therefore decided to use a blue dye to highlight any dysplastic epithelium. 10 mL of methylene blue 0.1% was administered through the working channel of the cholangioscope and then suctioned. As seen here, fibrinous exudates diffusely stained blue and were easy to distinguish from underlying erythematous ductal mucosa that did not stain with blue dye. The inflamed ductal mucosa in the body and tail appeared uniform with no identifiable focal abnormalities. We obtained random biopsies of the main pancreatic duct in the body and tail. In the neck of the pancreas, we noted a clear difference in the uptake of methylene blue between the IPMN, depicted by green arrows, and the uninvolved surrounding mucosa, depicted by white arrows. In addition, we observed a difference in the degree of blue dye uptake within the IPMN itself. While most of the lesion appeared to uptake the dye, there was a distinct central area that did not stain, depicted by the yellow arrows. Targeted biopsies were obtained from areas of the IPMN that stained blue and those that did not stain blue. In addition, we obtained biopsies from the non-staining and otherwise unremarkable areas surrounding the IPMN. Histopathology revealed main duct IPMN without dysplasia from the stained areas of the lesion and main duct IPMN with dysplasia from the non-staining central areas of the lesion. All other areas of the main pancreatic duct that did not uptake the dye revealed non-dysplastic ductal mucosa with benign inflammatory changes that were likely related to the pre-existing stent. The patient was referred to a pancreatic surgeon and a decision was made to proceed with the Whipple procedure instead of the previously planned total pancreatectomy. In this case report, methylene blue was helpful to better define the extent of main pancreatic ductal involvement in patients with main duct IPMN. To the best of our knowledge, this is the first reported case of in vivo dye-based pancreatoscopy using methylene blue. In this case, we were able to reliably distinguish between main duct IPMN that stained blue and chronically inflamed pancreatic ductal mucosa that did not stain. In addition, we were able to identify dysplastic areas within the main duct IPMN that had a similar morphological appearance as the rest of the lesion, but were visually distinct on pancreatoscopy due to a differential non-staining with methylene blue. Further studies are needed to evaluate efficacy and clinical utility. Thank you for your attention.

Chromopancreatoscopy

Intraductal pancreatic mucinous neoplasm

Methylene blue

Whipple procedure

Pancreatoscopy